Scientists Able To Slow Aging In Mice By Modifying The Brain’s Hypothalamus

When we age, all parts of our body deteriorate over time. But while aging as a whole might be an accumulation of disparate processes, scientists have long wondered if it might be controlled by some central location in the body. Researchers have now uncovered an area in the brain about the size of an almond in humans that wields powerful control over the body’s aging process. By manipulating a single substance secreted by the hypothalamus they were able to extend the lives of mice. The work opens up the possibility that the hypothalamus may be an important target in treating age-related diseases such as heart disease and Alzheimer’s.

The hypothalamus controls a number of hormones that influence development, growth, metabolism and reproduction. Previous research has also shown that an unhealthy hypothalamus can lead to disorders associated with aging such as glucose intolerance and hypertension. Researchers at Albert Einstein College of Medicine of Yeshiva University then asked if the hypothalamus might have some greater control over aging in general.

To answer this question they focused on a protein produced by the hypothalamus called NF-kB that regulates a wide variety of physiological processes including cell growth and death, and inflammation and has been connected to diseases such as cancer, neurodegenerative diseases, and heart disease. The researchers hypothesized that preventing NF-kB from being produced in the hypothalamus would slow the process of aging.

The lifespan of untreated, normal mice ranged between 600 and 1000 days. The mice who had their NF-kB blocked lived up to 1100 days, a median lifespan increase of 20 percent. In an assessment at six months of age they showed more muscle and bone, thicker skin, and performed better on learning tests than the normal mice.

Another substance important for whole-body aging is gonadotropin-releasing hormone (GnRH), which is important for our reproductive systems. Like NF-kB, GnRH is synthesized and released from the hypothalamus. It is also regulated by NF-kB – production of NF-kB leads to a decrease in GnRH. The authors therefore hypothesized that the anti-aging effects of NFkB may have been mediated through their effects on GnRH. If that’s true, then boosting the amount of GnRH should have similar anti-aging effects.

One hallmark of aging is decreased neurogenesis in the brain, particularly in the hypothalamus and in the brain’s memory center, the hippocampus. Injecting GnRH directly into the brain caused the sprouting of new neurons, not only in these areas but other areas of the brain where neurogenesis doesn’t normally occur. The GnRH even worked in old mice. As the hippocampus is important for learning and memory, it’s likely that the new neurons born here were behind the boost in learning performance seen in the mice who had their NF-kB blocked.

The study was published recently in the journal Nature.

“It’s clear from our study that many aspects of aging are controlled by the hypothalamus,” Dongsheng Cai, lead author of the study, said in a news release. “What’s exciting is that it’s possible – at least in mice – to alter signaling within the hypothalamus to slow down the aging process and increase longevity.”

In addition to increasing longevity, knocking down NF-kB levels might also one day be a strategy to combat neurodegenerative diseases associated with aging. Inflammation in the hypothalamus is associated with cognitive decline and age-related brain disorders. The team saw that inflammation was higher in old mice. But treating the mice with GnRH decreased the inflammation. So not only could life be extended through the new neurons produced when the amount of NF-kB is decreased, but through reduced inflammation as well.

We all know that, through the brain, we control our movements, sense our environment, and feel emotion. But it’s easy to forget that the brain also regulates the “behind the scenes” basics of our physiology. As it turns out, through controlling our body’s hormones the hypothalamus has control of systemic aging and our lifespans. Just the size of an almond, it’s a small area with enormous therapeutic potential.